dc.contributor.author | Byakwaga, Helen | |
dc.contributor.author | Boum II, Yap | |
dc.contributor.author | Huang, Yong | |
dc.contributor.author | Muzoora, Conrad | |
dc.contributor.author | Kembabazi, Annet | |
dc.contributor.author | Weiser, Sheri D | |
dc.contributor.author | Bennett, John | |
dc.contributor.author | Cao, Huyen | |
dc.contributor.author | Haberer, Jessica E | |
dc.contributor.author | Deeks, Steven G | |
dc.contributor.author | Bangsberg, David R | |
dc.contributor.author | McCune, Joseph M. | |
dc.contributor.author | Martin, Jeffrey N | |
dc.contributor.author | Hunt, Peter W | |
dc.date.accessioned | 2020-02-25T09:39:13Z | |
dc.date.available | 2020-02-25T09:39:13Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Byakwaga, H., Boum, Y., Huang, Y., Muzoora, C., Kembabazi, A., Weiser, S. D., ... & Bangsberg, D. R. (2014). The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral therapy. The Journal of infectious diseases, 210(3), 383-391. | en_US |
dc.identifier.uri | http://ir.must.ac.ug/xmlui/handle/123456789/512 | |
dc.description.abstract | Background. Human immunodeficiency virus (HIV) infection–induced indoleamine 2,3-dioxygenase-1 (IDO)
expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream
catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this
pathway in treated HIV disease is unknown.
Methods. We measured systemic IDO activity (calculated as the ratio of plasma levels of kynurenine to tryptophan; hereafter, the “KT ratio”) in HIV-infected Ugandans before and during antiretroviral therapy (ART)–mediated
viral suppression and its association with the rate of subsequent CD4+ T-cell count recovery and mortality.
Results. Among 435 participants, a higher pre-ART KT ratio was associated with a higher plasma virus load
(P < .001) and lipopolysaccharide level (P = .018), a lower CD4+ T-cell count (P < .001), and female sex (P = .047).
Through month 12 of ART-mediated viral suppression, the plasma KT ratio decreased by approximately 50%
(P < .001). After adjustment for pre-ART CD4+ T-cell count, virus load, age, and sex, a higher month 12 KT ratio
predicted a slower rate of subsequent CD4+ T-cell count recovery (P = .001). Thirty-nine participants died. After
adjustment for pre-ART CD4+ T-cell count, virus load, body mass index, sex, and age, a higher pre-ART and
month 6 KT ratio predicted increased mortality (P ≤ .016).
Conclusions. The kynurenine pathway of tryptophan catabolism independently predicts poor CD4+ T-cell
count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important
target for interventions. | en_US |
dc.description.sponsorship | This work was supported by the National Institutes
of Health (R56AI100765, R21AI078774, K24MH087227, K23MH087228,
T32AA007240, R01MH054907, P30AI27763, U19 AI96109, D43
CA153717, and P01 AI076174), the Doris Duke Charitable Foundation
(Clinical Scientist Development Award 2008047), and the Sullivan Family Foundation | en_US |
dc.language.iso | en | en_US |
dc.publisher | Oxford University Press | en_US |
dc.subject | Tryptophan | en_US |
dc.subject | kynurenine | en_US |
dc.subject | indoleamine 2,3-dioxygenase-1 | en_US |
dc.subject | HIV | en_US |
dc.subject | mortality | en_US |
dc.subject | antiretroviral therapy | en_US |
dc.subject | Uganda | en_US |
dc.title | The Kynurenine Pathway of Tryptophan Catabolism, CD4+ T-Cell Recovery, and Mortality Among HIV-Infected Ugandans Initiating Antiretroviral Therapy | en_US |
dc.type | Article | en_US |